Project/Area Number |
26462299
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | Okayama University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
大橋 俊孝 岡山大学, 医歯薬学総合研究科, 教授 (50194262)
川畑 智子 岡山大学, 大学病院, 助教 (90600669)
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | miRNA / 軟骨代謝 / メカニカルストレス / マイクロアレイ解析 / エピジェネティクス / HDAC / 疾患修飾性OA治療薬 / 新規疾患修飾性OA治療薬 / microRNA / 軟骨細胞 / ADAM12 / miR-29b |
Outline of Final Research Achievements |
Human chondro-osteophytes were obtained at the time of total joint arthroplasty from knee joints and hip joints of patients with osteoarthritis (OA). ADAM12, one of the target gene of miRNA29-b was observed in chondrocytes of the proliferative and hypertrophic zones in human chondro-osteophytes by immunohistochemistry. ADAM12 mRNA was up-regulated during chondrogenic differentiation in ATDC5 cells, before up-regulation of type X collagen mRNA. In patients with OA, mechanical forces acting on the sites of soft tissue attachments at the joint margins play a primary role in chondro-osteophyte formation and may cause joint pain leading to impaired activity of daily living. In addition, it has been reported that the haplotypes in the ADAM12 gene are strongly related to the risk of clinical knee OA. Modulation of signaling pathway of miRNA29b-ADAM12 axis may contribute the future development of a novel therapy against OA.
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